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- 저자 : Kaur Simran Deep (검색결과 1 건)
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Singh Gurdeep,Singh Davinder,Choudhari Manisha,Kaur Simran Deep,Dubey Sunil Kumar,Arora Saroj,Bedi Neena 한국약제학회 2021 Journal of Pharmaceutical Investigation Vol.51 No.6
Purpose The present study aimed to develop a novel therapeutic approach for controlled delivery of exemestane (EXE) to cancer cells using nanostructured polymeric micelles. Methods A simplex centroid design of experiment study was employed for optimizing the polymeric micelle formulation to achieve the desired critical quality attributes, including micelle size, drug loading (DL), encapsulation efficiency (EE), and critical micelle concentration (CMC). The oil-in-water (o/w) solvent evaporation method was used to prepare mixed micelles (MMs) of copolymers L121/F127/GL44 for encapsulating EXE. Profile analysis tensiometer methods were used to determine the CMC of the copolymer mixture. EXE-MMs, blank mixed micelles, and lyophilized mixed micelles (Lyp- EXE-MMs) were characterized for other key quality attributes, such as zeta potential, chemical interactions, and morphology. Results The optimized ratio of L121/F127/GL44 was 1.98, 0.812, and 1.20, respectively, providing EXE-MMs with small micelle sizes (35.45 ± 1.20 nm), higher EE (89.75 ± 2.14%), and DL (5.85 ± 2.14%). EXE-encapsulated MMs exhibited an in vitro sustained release profile with improved cytotoxicity against MCF-7 cells than that with pure EXE. The cellular growth inhibitory concentration ( IC50) of EXE-MMs was 0.225 ± 0.124 μg/ml, while that of naïve EXE was 7.58 ± 0.145 μg/ ml. Moreover, in vivo pharmacokinetic parameters of EXE micellar formulation showed significant improvement in Cmax and AUC (0–72 h), viz. 207.54 ± 18.65 ng/ml and 3530.77 ± 212.25 ng h/ml, respectively, suggesting enhanced bioavailability than that of pure EXE. Conclusion EXE-MMs have a great potential for enhancing the bioavailability of EXE.
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